Spontaneous tumour lysis syndrome associated with non-Hodgkin's lymphoma--a case report.

Spontaneous tumour lysis syndrome is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, metabolic acidosis and hypocalcemia, that occur even prior to the treatment of a neoplasm. This rare occurrence was encountered in a patient with non-Hodgkin's lymphoma (NHL), of follicular cell type. Conservative but intensive treatment led to complete resolution. Subsequent chemotherapy was well tolerated.

Methyl p-hydroxyphenyllactate and nuclear type II binding sites in malignant cells: metabolic fate and mammary tumor growth.

Previous studies in our laboratory demonstrated that methyl p-hydroxyphenyllactate (MeHPLA) is an important cell growth-regulating agent which binds to nuclear type II binding sites in normal and malignant cells. Furthermore, this compound is deficient in a variety of rat and mouse mammary tumors and human breast cancer preparations, and this deficiency correlates with the loss of regulatory control. The present studies were performed to examine the metabolic fate of [3H]MeHPLA in mouse mammary tumors. Stable analogs of this compound such as 4,4'-dihydroxy benzylidene acetophenone were also assessed for nuclear type II site binding affinity and their ability to inhibit mammary cancer cell growth and proliferation in vitro and in vivo. The results demonstrate that mouse mammary tumors contain esterase activity which hydrolyzes MeHPLA to p-hydroxyphenyllactic acid, and this was the only major metabolite detected in these tumor preparations in vitro or in vivo. 4,4'-Dihydroxy benzylidene acetophenone, an esterase-stable MeHPLA analog, was found to bind with high affinity to nuclear type II sites but not the estrogen receptor, was capable of occupying type II sites in cultured MCF-7 cells, and inhibited the proliferation of these cells in concentrations which directly correlated with type II binding site occupancy. Similarly, 4,4'-dihydroxy benzylidene acetophenone administration by silastic implant or injection resulted in a dose-dependent inhibition of the growth of transplantable mammary tumors in mice, suggesting that this stable analog mimicks MeHPLA as a cell growth-regulating agent. Taken together, these results suggest esterase hydrolysis of MeHPLA in mammary tumors may result in a deficiency in this compound which correlates with a loss of regulatory control.

Nuclear type II sites and malignant cell proliferation: inhibition by 2,6-bis-benzylidenecyclohexanones.

Methyl-p-hydroxyphenyllactate (MeHPLA) is a bioflavonoid and/or tyrosine metabolite which may regulate cellular growth and proliferation through interactions with nuclear type II sites. Our current studies suggest that type II sites may function as MeHPLA receptors which are localized on the nuclear matrix, and occupancy of this binding site by MeHPLA directly correlates with the inhibition of normal and malignant cell proliferation. This ligand is inactivated by MeHPLA esterase in mammary tumors, resulting in a deficiency in MeHPLA, high quantities of unoccupied type II sites, and uncontrolled cellular proliferation. For these reasons we synthesized 2,6-bis((3,4-dihydroxyphenyl)methylene)-cyclohexanone (BDHPC) and 2,6-bis((3-methoxy-4-hydroxyphenyl)-methylene)cyclohexanone (BMHPC) for assessment as nuclear type II site and cell growth antagonists. These two esterase stable cyclohexanone derivatives, which bind to nuclear type II sites with high affinity (Kd 1-7 nM), mimic MeHPLA as cell growth-regulating agents. Dose-dependent occupancy of type II sites in MCF-7 human cells by BDHPC and BMHPC directly correlated with the inhibition of cell proliferation, and administration of BDHPC by silastic implant inhibited mouse mammary tumor growth in vivo. These findings demonstrate that esterase-stable type II antagonists such as BDHPC and BMHPC inhibit mammary cancer cell proliferation in vitro and in vivo and support earlier studies demonstrating that MeHPLA and functionally related compounds may regulate malignant cell proliferation at the level of this binding site.

On arabinose as a component of brain hyaluronate. Confirmation by chromatographic, enzymatic and chemical ionization-mass spectrometric analyses.

The controversy about the presence of the pentose arabinose in brain hyaluronate was reinvestigated using modern analytical tehcnics. The purified bovine brain hyaluronate contained the neutral sugars: arabinose, 0.18%; glucose, 0.05%; and fucose, 0.22%. The confirmation of the presence of arabinose was obtained by paper and thin layer chromatography of the neutral sugars in deionized hyaluronate hydrolysate. Gas-liquid chromatography of the aldononitrile peracetate of the pentose isolated by preparative paper chromatography gave a single distinct peak, corresponding to standard arabinose on three columns packed with three different phases. Chemical ionization data and mass spectrum of the aldononitrile peracetate derivative agreed with those of the authentic arabinonitrile tetracetate. Analysis of the isolated pentose with the help of the enzymes L-arabinose isomerase and L-ribulose kinase, which are specific for their substrates, further established its identity as L-arabinose.

Human umbilical cord hyaluronate. Neutral sugar content and carbohydrate-protein linkage studies.

Paper chromatography of neutral sugars and gas chromatography of their aldononitrile acetates indicated the presence of fucose, arabinose and a small amount of glucose in purified human umbilical cord hyaluronate. The molar ratios of serine, threonine and aspartic acid to neutral sugars were not unity, suggesting the non-involvement of the neutral sugars and the amino acids in a carbohydrate-protein linkage. The same was indicated by an increase in the percentage of the aforementioned amino acids and by the absence of sugar alditols in umbilical cord hyaluronate reduced eith NaBH4 -PdCl2, after alkali treatment. This reduction caused a decrease in the intrinsic viscosity and molecular wieght to about one-half and an appreciable decrease in the specific rota tion of hyaluronate, suggesting a separation of the two antiparallel chains o the double helical hyaluronate. The umbilical cord hyluronate containe contained bound silicon and it is possible that this bound silicon may cross-link the two chains at interspersed intervals through the uronic acid moiety and/or through neutral sugars.

Growth inhibitory effects of bioflavonoids and related compounds on human leukemic CEM-C1 and CEM-C7 cells.

Seven compounds, which included some naturally occurring dietary substances, were tested for their inhibitory effects on growth and metabolism of human leukemic CEM-C1 and CEM-C7 cell lines. Among the active compounds the naturally occurring dietary constituents were found to be the most active. The strongest inhibitory effects were observed with 3',4',5,7-tetrahydroxy-flavone (luteolin) and 4,4'-dihydroxychalcone. 31P-NMR spectra of cells incubated for 24 h with 30 microM of either of these compounds show complete ATP depletion. Also glucose uptake by the cells as measured by 13C-NMR is completely inhibited by these compounds. These results may be relevant to the tumor suppressing activity of bioflavonoids and the role of these compounds in chemoprevention.

Microwave-accelerated solvent-free synthesis of thioketones, thiolactones, thioamides, thionoesters, and thioflavonoids.

[reactions: see text] An expeditious, solvent-free, and high yield conversion of ketones, flavones, isoflavones, lactones, amides, and esters to the corresponding thio analogues is described utilizing Lawesson's reagent in a process that circumvents the use of dry solvents and excess of the reagent.

Hybridization of DNA targets to glass-tethered oligonucleotide probes.

Hybridization of nucleic acids to surface-tethered oligonucleotide probes has numerous potential applications in genome mapping and DNA sequence analysis. In this article, we describe a simple standard protocol for routine preparation of terminal amine-derivatized 9-mer oligonucleotide arrays on ordinary microscope slides and hybridization conditions with DNA target strands of up to several hundred bases in length with good discrimination against mismatches. Additional linker arms separating the glass surface from the probe sequence are not necessary. The technique described here offers a powerful tool for the detection of specific genetic mutations.

Catalyst-free reactions under solvent-free conditions: microwave-assisted synthesis of heterocyclic hydrazones below the melting points of neat reactants.

The reaction of neat 5- or 8-oxobenzopyran-2(1H)-ones, 1-3, with a variety of aromatic and heteroaromatic hydrazines, 4, is remarkably accelerated upon irradiation in a household microwave oven in the absence of any catalyst, solid support or solvent thus providing an environmentally friendly route to several heterocyclic hydrazones.

Serum and mucopolysaccharide (glycosaminoglycans) levels in psychiatric patients.

Serum acid glycosaminoglycans (GAG) levels were measured in 50 normals and 177 samples from different types of psychiatric patients. Mean levels were significantly higher in paranoid type schizophrenia, organic brain syndrome associated psychosis and manic type manic-depressive psychosis. The levels returned to slightly above the normal range upon partial remission in paranoid schizophrenics. In catatonic and hebephrenic schizophrenias the values were in the upper part of normal range. The levels were either in upper normal range or slightly higher in non-psychotic organic brain syndrome. In depressed type manic depressive psychosis levels were either lower than normal or in the lower part of normal range.

Beta-glucuronidase in sera of patients with epileptic seizure activity, diabetes and some other disease states.

As compared to controls and epileptics with controlled seizures, serum beta-glucuronidase enzyme is elevated significantly in epileptics with uncontrolled seizures. The enzyme begins to rise just before the seizure, remains elevated during, and for some time after the seizure and then begins to decline, unless another seizure follows the first seizure. The enzyme is not elevated in controlled diabetes patients without any secondary complications. But the enzyme is also elevated in other pathological conditions which involve increased connective tissue catabolism. However, the enzyme is elevated constantly and all the time in these conditions, in contrast with its elevation in uncontrolled epilepsy only close to the seizures.

Antiviral, antibacterial, and antifungal activities of isatin N-Mannich bases.

Preliminary antiviral, antibacterial, and antifungal screening results of a series of isatin N-Mannich bases are provided.

Effects of nitric oxide donors on the retinal function measured with electroretinography.

It has been reported that nitric oxide raises c-GMP in the vascular muscle to cause vasodilation and to improve blood flow in the retina. Consequently, a diverse group of potential nitric oxide (NO) donors were synthesized and evaluated for their effectiveness in improving the retinal function after ischemic insult. These compounds include an NO carrier, N-acetyl-S-nitrosoglutathione (RVC-593), several NO donors such as N-nitropyrazole derivatives (RVC-595, RVC-596, RVC-597, RVC-598, and RVC-599) and two fused N-heterocycles, 4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxides, (RVC-600 and RVC-601). Most of the compounds demonstrated the pharmacological activity in the ophthalmic model, except the pyrazole derivatives (RVC-595, RVC-596 and RVC-599) that bear bulky aromatic substituents at the R2-position.

Improvement of retinal functions after ischemia with L-arginine and its derivatives.

Retinal ischemia was created by occlusion of rat central retinal artery for 30 minutes. The loss of retinal function was indicated by the loss of b-wave of electroretinogram. The recovery of retinal function after reperfusion of central retinal artery was observed with the gradual recovery of b-wave amplitude to approximately 20% of original b-wave amplitude. When L-arginine (RVC-579) was administered at the time of retina ischemia, the b-wave amplitudes recovered up to 64% of original height and were significantly higher than corresponding controls at 120, 180, and 240 min after ischemia. When the derivative of L-arginine, N alpha-benzoyl-L-arginine ethyl ester (RVC-578), was administered, the b-wave recovery was significantly higher than corresponding controls at 90, 120, 180, and 240 min after ischemia; the recovery reached 51% of the original b-wave value. These results indicate that the L-arginine and its lipophilic derivatives could be used for the treatment of ischemic retinopathy. Since L-arginine is a natural amino acid, it is not expected to produce major side effects, if any, and could pave the way for the development of a safer drug to be used in the clinics. Compounds which increase the formation of NO in vivo, dilate blood vessels. Both L-arginine and RVC-578 can be placed in this category. They may improve effects of retinal ischemia by increasing NO production.

Ocular hypotensive effects of L-arginine and its derivatives and their actions on ocular blood flow.

Effects of L-arginine and some related compounds on the intraocular pressure recovery (IOPR) and ocular blood flow in rabbits had been studied. It was found that L-arginine (RVC-579) and N alpha-benzoyl-L-arginine ethyl ester (RVC-578) delayed the IOPR markedly: The IOPR of the contralateral non-treated eye was delayed to the same extent as the treated eye. The effects of closely related congeners L-(+)-canavanine (RVC-581) and L-homoarginine (RVC-580) on the IOPR were qualitatively similar to RVC-579 and RVC-578 but less effective. RVC-578 was found to increase the blood flow significantly in ciliary body, retina and choroid. On the other hand, NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, reduced the blood flow in choroid at 60 and 120 min after drug administration and did not increase the blood flow in iris, ciliary body and retina. These results indicate that L-arginine and its derivative are capable of lowering the IOP possibly through the formation of nitric oxide to relax the blood vessel and to reduce the IOP as a result.

Nitric oxide donors: effects of S-nitrosoglutathione and 4-phenyl-3-furoxancarbonitrile on ocular blood flow and retinal function recovery.

It is known that NO is involved in the regulation of intraocular pressure (IOP) and retinal function recovery after ischemia. Thus, S-nitrosoglutathione (RVC-588) and 4-phenyl-3-furoxancarbonitrile (RVC-589) as NO donor and precursor, respectively, were studied in terms of their ability to increase b-wave recovery of electroretinogram (ERG) and ocular blood flow. It was found that RVC-588 increased b-wave amplitude markedly from 28% (control) to 67% (treated) and the blood flow significantly in the retina, choroid, and ciliary body. In the case of RVC-589, the b-wave recovery was significantly increased from 30% (control) to 51% (treated) but was less marked than that of RVC-588. The blood flow in the eye tissues was not significantly increased by RVC-588, but there was a clear tendency to enhance in the retina, choroid and iris. These results indicate that NO can be released effectively from S-nitrosothiols but less significantly from furoxans.

Prevalence of left atrial thrombus in rheumatic mitral stenosis with atrial fibrillation and its response to anticoagulation: a transesophageal echocardiographic study.

BACKGROUND: The frequency of occurrence of left atrial thrombi, and the effect of anticoagulation in patients with rheumatic mitral stenosis and atrial fibrillation is not well established. This study was conducted to evaluate the occurrence of left atrial body and left atrial appendage clots in patients with rheumatic mitral stenosis and atrial fibrillation, and to document the effect of long-term anticoagulation on clot dissolution. METHODS AND RESULTS: Consecutive patients with severe rheumatic mitral stenosis and atrial fibrillation were assessed by transesophageal echocardiography. Those with left atrial body or left atrial appendage clots were anticoagulated with oral nicoumalone. Transesophageal echocardiography was then repeated in patients on anticoagulation who were on regular follow-up, and in whom percutaneous transvenous mitral commissurotomy could be considered. Of the 490 patients studied, 163 had left atrial body or left atrial appendage clots. A repeat transesophageal echocardiographic examination was done in 50 patients who had optimal anticoagulation for a period of 6 months. Only 2 of the 17 patients who had left atrial body clots had successful clot dissolution after long-term anticoagulation, while the left atrial appendage clots disappeared in 31 of 33 patients (p<0.001). CONCLUSIONS: Left atrial clots are present in a third of patients with severe rheumatic mitral stenosis and atrial fibrillation. Isolated left atrial appendage clots in patients with rheumatic mitral stenosis and atrial fibrillation can disappear with long-term anticoagulation, while thrombi that extend into the left atrial body may persist despite optimal anticoagulation.

Supravalvular aortic stenosis and coronary ostial stenosis in homozygous familial hypercholesterolemia.

Patients with homozygous familial hypercholesterolemia exhibit severe hypercholesterolemia, cutaneous and tendon xanthomata, and premature atherosclerosis from childhood. A rare presentation of this condition with supravalvular aortic stenosis and coronary ostial stenosis is described.

Synthesis of 4-(3-benzazolymethyl)aminodiphenyl ethers and other related products as potential antimicrobial agents.

4-Aminodiphenyl ethers (2) obtained by reducing the corresponding nitro analogue (1), have been incorporated into benzazoles, phthalimides and 4-quinazolone in the presence of 40% formalin to furnish a series of 4-(3-benzazolymethyl)aminodiphenyl ethers (3) under the conditions of the Mannich reaction. In an alternate procedure, 3 were obtained on refluxing the N-hydroxymethyl derivatives of benzazoles etc. with 2 in methanol. A few amine exchange reactions were also performed and the stability of a few representative compounds was studied in different acidic media. The antibacterial spectrum of all the synthesized compounds was determined against Bacillus subtilis as well as Bacillus pumilus by the agar diffusion technique.

Evaluation of vanillic acid analogues as a new class of antifilarial agents.

A number of vanillic acid analogues (1-14) have been synthesised and evaluated against experimental filarial infections using cotton rats (Sigmodon hispidus) infected with Litomosoides carinii, a primary screening model, at a dose of 30 mg/kg, ip for 5 days. Of the 8 compounds tested, 4 (5,7, 11 and 12) exhibited high micro- and macro-filaricidal activity with sterilization of surviving female worms. Compounds 5, 7, 12 showed remarkable adulticidal action (> 80%). Sterilization of the female worms by compounds 11 and 12 was highly significant (80-100%).